Girotto, GiorgiaScheffer, Déborah I.Morgan, AnnaVozzi, DiegoRubinato, ElisaDi Stazio, MariateresaMuzzi, EnricoPensiero, StefanoGiersch, AnneCorey, DavidGasparini, Paolo2016-01-042015Girotto, G., D. I. Scheffer, A. Morgan, D. Vozzi, E. Rubinato, M. Di Stazio, E. Muzzi, et al. 2015. “PSIP1/LEDGF: a new gene likely involved in sensorineural progressive hearing loss.” Scientific Reports 5 (1): 18568. doi:10.1038/srep18568. http://dx.doi.org/10.1038/srep18568.2045-2322http://nrs.harvard.edu/urn-3:HUL.InstRepos:23993508Hereditary Hearing Loss (HHL) is an extremely heterogeneous disorder. Approximately 30 out of 80 known HHL genes are associated with autosomal dominant forms. Here, we identified PSIP1/LEDGF (isoform p75) as a novel strong candidate gene involved in dominant HHL. Using exome sequencing we found a frameshift deletion (c.1554_1555del leading to p.E518Dfs*2) in an Italian pedigree affected by sensorineural mild-to-moderate HHL but also showing a variable eye phenotype (i.e. uveitis, optic neuropathy). This deletion led to a premature stop codon (p.T519X) with truncation of the last 12 amino acids. PSIP1 was recently described as a transcriptional co-activator regulated by miR-135b in vestibular hair cells of the mouse inner ear as well as a possible protector against photoreceptor degeneration. Here, we demonstrate that it is ubiquitously expressed in the mouse inner ear. The PSIP1 mutation is associated with a peculiar audiometric slope toward the high frequencies. These findings indicate that PSIP1 likely plays an important role in HHL.en-USJournal Article2016-01-0410.1038/srep18568